Freeze-fracture analysis of epithelial cell lysosomal inclusions in Crohn's disease

Ileal epithelial cells from patients with Crohn's disease contain many large electron-dense lysosomal granules. Freeze-fracture electron microscopy was utilized to evaluate granule membrane ultrastructure and the interaction between granule contents and granule-limiting membranes. Large apical granules contained 0.1-0.6 micron vesicular inclusions as well as whorl-like myelin figures. The P-fracture face contained discrete membrane specializations on the granule surface that were composed of circular arrays of intramembranous particles. Areas of membrane devoid of intramembranous particles were also seen. These circular arrays and particle-poor regions resemble previously documented areas of membrane fusion. These results are discussed and a number of possible interpretations for their significance in terms of the pathogenesis of Crohn's disease are presented.